During T cell development, thymocytes that are able to recognize self MHC are signalled to mature (positive selection), whereas those capable of self reactivity are selected to die (negative selection). Many of these studies deal with the paradox of how signaling resulting from a specific TCR-MHC interaction can determine the positive or negative selection events. Several investigations involving TCR transgenic mice reveal that distinct thymic antigen presenting cells are probably not responsible for these alternate forms of selection. Instead, they suggest that it is the affinity of the TCR-MHC interaction that controls the developmental outcome. Increasing the coreceptor expression (through a CD8 transgene) is able to enhance TCR recognition of MHC, and alter net selection effects from positive to negative. Likewise, enhancing MHC expression by increasing MHC gene dosage can alter developmental fate. Thymic selection can, in some cases, be determined also by tissue-specific peptides presented only on thymic epithelium. Our previous studies indicated that the thymus is able to induce tolerance to self antigens not only by deletional mechanisms but also by clonal inactivation (anergy). Transfer of the nonresponsive cells into hosts that lack the self antigen or into in vitro culture results in a reversal of the nonresponsive state, indicating that antigen is required to maintain this nondeletional form of in vivo tolerance. The mechanism responsible for commitment to the alphaBeta or gamma delta lineage has also been approached using TCR transgenic mice. If TCR-beta transcriptional regulatory elements are used to direct expression of the TCRalphaBeta transgenes, gamma delta T cells do not appear. Instead, there appears a CD4-8- cell bearing the TCR-alphaBeta transgenic receptor, but with the developmental, phenotypic, and functional properties of gamma delta T cells. These results suggest that T cell functions may be associated with a specific lineage, irrespective of TCR usage. These findings have led to an investigation of the role of TCR transcriptional regulatory elements in lineage development.